[Network Meta-analysis of efficacy of seven Chinese patent medicines in treatment of inflammatory response in chronic glomerulonephritis].

This study aimed to evaluate the efficacy and safety of various Chinese patent medicines in the treatment of inflammatory response in chronic glomerulonephritis(CGN) based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicines for improving inflammatory response in patients with CGN was retrieved from databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to March 2023. All investigators independently screened the literature, extracted data, and evaluated the quality. Stata 16.0 and RevMan 5.4.1 software were used to analyze the data of the literature that met the quality standards. Finally, 71 RCTs were included, involving 7 Chinese patent medicines. The total sample size was 6 880 cases, including 3 441 cases in the test group and 3 439 cases in the control group. The network Meta-analysis showed that(1) in terms of reducing TNF-α, the top 3 optimal interventions according to the surface under the cumulative ranking curve(SUCRA) were Shenyanshu Capsules/Granules/Tablets+conventional western medicine, Huangkui Capsules+conventional western medicine, and Bailing Capsules+conventional western medicine.(2) In terms of reducing hs-CRP, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Huangkui Capsules+conventional wes-tern medicine, and Bailing Capsules+conventional western medicine.(3) In terms of reducing IL-6, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Bailing Capsules+conventional western medicine, and Shenyan Kangfu Tablets+conventional western medicine.(4) In terms of reducing 24hUTP, the top 3 optimal interventions according to SUCRA were Shenyan Kangfu Tablets+conventional western medicine, Bailing Capsules+conventional western medicine, and Huangkui Capsules+conventional western medicine.(5) In terms of reducing Scr, the top 3 optimal interventions according to SUCRA were Bailing Capsules+conventional western medicine, Shenyanshu Capsules/Granules/Tablets+conventional western medicine, and Yishen Huashi Granules+conventional western medicine.(6) In terms of reducing BUN, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Shenyanshu Capsules/Granules/Tablets+conventional western medicine, and Bailing Capsules+conventional western medicine.(7) In terms of improving the clinical total effective rate, the top 3 optimal interventions according to SUCRA were Huangkui Capsules+conventional western medicine, Kunxian Capsules+conventional western medicine, and Yishen Huashi Granules+conventional western medicine. The results showed that the combination of conventional western medicine and Chinese patent medicine could reduce the expression of serum inflammatory factors TNF-α, hs-CRP, and IL-6 and inhibit the inflammatory response. The combination of conventional western medicine and Chinese patent medicine was superior to conventional western medicine alone in reducing Scr, BUN, and 24hUTP, and improving the clinical total effective rate of treatment. Due to the limitation of the quantity and quality of literature included, the above conclusions need to be validated by more high-quality studies.

[Network Meta-analysis of efficacy of Chinese patent medicine in treatment of inflammatory response in diabetic nephropathy].

This study aimed to evaluate the efficacy and safety of various Chinese patent medicines in the treatment of inflammatory response in diabetic nephropathy(DN) based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicines for improving inflammatory response in patients with DN was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from database inception to October 2022. All investigators independently screened the literature, extracted data, and evaluated the quality. Stata 16.0 software and RevMan 5.4.1 were used to analyze the data of the literature that met the quality standards. Finally, 53 RCTs were included, involving 6 Chinese patent medicines. The total sample size was 4 891 cases, including 2 449 cases in the test group and 2 442 cases in the control group. The network Meta-analysis showed that(1) in terms of reducing TNF-α, the top 3 optimal interventions according to the surface under the cumulative ranking curve(SUCRA) were Shenshuaining Capsules/Granules/Tablets + conventional western medicine, Jinshuibao Capsules + conventional western medicine, and Niaoduqing Granules + conventional western medicine.(2) In terms of reducing hs-CRP, the top 3 optimal interventions according to SUCRA were Bailing Capsules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Shenshuaining Capsules/Granules/Tablets + conventional western medicine.(3) In terms of reducing IL-6, the top 3 optimal interventions according to SUCRA were Bailing Capsules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Jinshuibao Capsules + conventional western medicine.(4) In terms of reducing UAER, the top 3 optimal interventions according to SUCRA were Shenshuaining Capsules/Granules/Tablets + conventional western medicine, Huangkui Capsules + conventional western medicine, and Jinshuibao Capsules + conventional western medicine.(5) In terms of reducing Scr, the top 3 optimal interventions according to SUCRA were Jinshuibao Capsules + conventional western medicine, Niaoduqing Granules + conventional wes-tern medicine, and Tripterygium Glycosides Tablets + conventional western medicine.(6) In terms of reducing BUN, the first 3 optimal interventions according to SUCRA were Niaoduqing Granules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Huangkui Capsules + conventional western medicine.(7) In terms of improving the clinical total effective rate, the first 3 optimal interventions according to SUCRA were Jinshuibao Capsules + conventional western medicine, Niaoduqing Granu-les + conventional western medicine, and Huangkui Capsules + conventional western medicine. The results showed that the combination of western medicine and Chinese patent medicine could reduce the expression of serum inflammatory factors TNF-α, hs-CRP, and IL-6 and inhibit the inflammatory response. The combination of western medicine and Chinese patent medicine was superior to western medicine alone in reducing Scr, BUN, and UAER, and improving the total effective rate of treatment. Due to the limitation of the quantity and quality of literature included, the above conclusions need to be validated by more high-quality studies.

Potential molecular mechanisms of Ermiao san in the treatment of hyperuricemia and gout based on network pharmacology with molecular docking.

A network pharmacology integrated molecular docking strategy was used to predict the underlying molecular mechanism of Ermiao san in the treatment of hyperuricemia and gout. Traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform were used to screen out the active compounds and their targets of Ermiao san. The disease target genes related to hyperuricemia (HUA) and gout were obtained by searching CTD, DisGeNET, DrugBank, GeneCards, OMIM, TTD, and PharmGKB databases with "Hyperuricemia" and "Gout" as keywords, respectively. The potential targets of Ermiao san in the treatment of HUA and gout were screened through a Venn diagram. The protein-protein interaction network was constructed using Cytoscape software. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were then conducted. Finally, some compounds and core targets were selected for molecular docking verification by Autodock Vina and Pymol software. Forty-six active compounds, such as quercetin, wogonin and beta-sitosterol, etc were identified. Ermiao san plays a therapeutic role in HUA and gout regulating various biological processes, cellular compounds, and molecular functions. The core targets of Ermiao san for treating HUA and gout are AT1 (namely Protein Kinase Bα), interleukin-1 beta, prostaglandin-endoperoxide synthase 2, JUN, etc. And the key pathways are nuclear factor-κB, interleukin-17 and tumor necrosis factor. The results of molecular docking analyses suggested that active compounds of Ermiao san could bind well to the core protein receptors. Ermiao san has a synergistic mechanism of multiple compounds, multiple targets, and multiple pathways in the treatment of HUA and gout, which provides a good theoretical basis for the clinical application.

Multiphase convolutional dense network for the classification of focal liver lesions on dynamic contrast-enhanced computed tomography.

BACKGROUND: The accurate classification of focal liver lesions (FLLs) is essential to properly guide treatment options and predict prognosis. Dynamic contrast-enhanced computed tomography (DCE-CT) is still the cornerstone in the exact classification of FLLs due to its noninvasive nature, high scanning speed, and high-density resolution. Since their recent development, convolutional neural network-based deep learning techniques has been recognized to have high potential for image recognition tasks. AIM: To develop and evaluate an automated multiphase convolutional dense network (MP-CDN) to classify FLLs on multiphase CT. METHODS: A total of 517 FLLs scanned on a 320-detector CT scanner using a four-phase DCE-CT imaging protocol (including precontrast phase, arterial phase, portal venous phase, and delayed phase) from 2012 to 2017 were retrospectively enrolled. FLLs were classified into four categories: Category A, hepatocellular carcinoma (HCC); category B, liver metastases; category C, benign non-inflammatory FLLs including hemangiomas, focal nodular hyperplasias and adenomas; and category D, hepatic abscesses. Each category was split into a training set and test set in an approximate 8:2 ratio. An MP-CDN classifier with a sequential input of the four-phase CT images was developed to automatically classify FLLs. The classification performance of the model was evaluated on the test set; the accuracy and specificity were calculated from the confusion matrix, and the area under the receiver operating characteristic curve (AUC) was calculated from the SoftMax probability outputted from the last layer of the MP-CDN. RESULTS: A total of 410 FLLs were used for training and 107 FLLs were used for testing. The mean classification accuracy of the test set was 81.3% (87/107). The accuracy/specificity of distinguishing each category from the others were 0.916/0.964, 0.925/0.905, 0.860/0.918, and 0.925/0.963 for HCC, metastases, benign non-inflammatory FLLs, and abscesses on the test set, respectively. The AUC (95% confidence interval) for differentiating each category from the others was 0.92 (0.837-0.992), 0.99 (0.967-1.00), 0.88 (0.795-0.955) and 0.96 (0.914-0.996) for HCC, metastases, benign non-inflammatory FLLs, and abscesses on the test set, respectively. CONCLUSION: MP-CDN accurately classified FLLs detected on four-phase CT as HCC, metastases, benign non-inflammatory FLLs and hepatic abscesses and may assist radiologists in identifying the different types of FLLs.

Activity of fibroblast-like synoviocytes in rheumatoid arthritis was impaired by dickkopf-1 targeting siRNA.

BACKGROUND: Fibroblast-like synoviocytes (FLSs), resident mesenchymal cells of synovial joints, play an important role in the pathogenesis of rheumatoid arthritis (RA). Dickkopf-1 (DKK-1) has been proposed to be a master regulator of bone remodeling in inflammatory arthritis. Here, potential impairation on the activity of FLSs derived from RA to small interfering RNAs (siRNAs) targeting DKK-1 was investigated. METHODS: siRNAs targeting DKK-1 were transfected into FLSs of patients with RA. Interleukin (IL)-1ß, IL-6, IL-8, matrix metalloproteinase (MMP) 2, MMP3, MMP9, transforming growth factor (TGF)-ß1, TGF-ß2 and monocyte chemoattractant protein (MCP)-1 levels in the cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Invasion assay and H incorporation assay were utilized to investigate the effects of siRNAs targeting DKK-1 on FLSs invasion and cell proliferation, respectively. Western blotting was performed to analyze the expression of nuclear factor (NF)-κB, interleukin-1 receptor-associated kinase (IRAK)1, extracellular regulated protein kinases (ERK)1, Jun N-terminal kinase (JNK) and ß-catenin in FLSs. RESULTS: DKK-1 targeting siRNAs inhibited the expression of DKK-1 in FLSs (P < 0.01). siRNAs induced a significant reduction of the levels of IL-6, IL-8, MMP2, MMP3 and MMP9 in FLSs compared to the control group (P < 0.05). DKK-1 targeting siRNAs inhibited the proliferation and invasion of FLSs (P < 0.05). Important molecules of pro-inflammatory signaling in FLSs, including IRAK1 and ERK1, were decreased by the inhibition of DKK-1 in FLSs. In contrast, ß-catenin, a pivotal downstream molecule of the Wnt signaling pathway was increased. CONCLUSIONS: By inhibiting DKK-1, we were able to inhibit the proliferation, invasion and pro-inflammatory cytokine secretion of FLSs derived from RA, which was mediated by the ERK or the IRAK-1 signaling pathway. These data indicate the application of DKK-1 silencing could be a potential therapeutic approach to RA.

GP205, a new hepatitis C virus NS3/4A protease inhibitor, displays higher metabolic stability in vitro and drug exposure in vivo.

NS3/4A serine protease is a prime target for direct-acting antiviral therapies against hepatitis C virus (HCV) infection. Several NS3/4A inhibitors have been widely used in clinic, while new inhibitors with better characteristics are still urgently needed. GP205 is a new macrocyclic inhibitor of NS3/4A with low nanomolar activities against HCV replicons of genotypes 1b, 2a, 4a, and 5a, with EC50 values ranging from 1.5 to 12.8 nmol/L. In resistance selection study in vitro, we found resistance-associated substitutions on D168: The activity of GP205 was significantly attenuated against 1b replicon with D168V or D168A mutation, similar as simeprevir. No cross resistance of GP205 with NS5B or NS5A inhibitor was observed. Combination of GP205 with sofosbuvir or daclatasvir displayed additive or synergistic efficacy. The pharmacokinetic profile of GP205 was characterized in rats and dogs after oral administration, which revealed good drug exposure both in plasma and in liver and long plasma half-life. The in vitro stability test showed ideal microsomal and hepatic cells stability of GP205. The preclinical profiles of GP205 support further research on this NS3/4A inhibitor to expand the existing HCV infection therapies.

Snapshot of HIV pathogenesis in China.

Several reviews have focused on the nature of HIV infection and its spread in various geographical regions of China. In contrast, this review provides a comprehensive update on the prevalence of multiple HIV-1 subtypes, consequent emergence of recombinant and novel forms of HIV-1 in China, and the implications this may have on HIV diversity and the development of effective vaccines. In addition it also examines the dissemination of primary drug resistance in therapy naïve patients, as well as co-infections with two other important viruses-hepatitis B and C. The main purpose of this review is to provide a current snapshot of HIV-1 pathogenesis in China and possibly shed some light on the future of HIV evolution, and potential challenges for future vaccine and anti-retroviral therapeutics against HIV strains in this area.

[Study on the distribution of human immunodeficiency virus-1 subtypes in different regions of China and mother-to-child transmission].

OBJECTIVE: To study the distribution of human immunodeficiency virus (HIV)-1 genotypes in major prevalent regions of China and to illustrate the relationship between HIV-1 subtypes and mother-to-child transmission in a retrospective cohort. METHODS: HIV-1 gag p17 and env C2-V4 region were amplified by nested-polymerase chain reaction (nPCR) and the sequences were obtained by sequencing gag nPCR products or clones of env gene. RESULTS: 60 HIV-1 positive individuals were subject to typing for gag p17 and 69 for env C2-V4 region. Single clade was only found in Henan (subtype B') and Xinjiang (subtype C), and subtypes C and E were demonstrated in Yunnan. These regions represented most of the HIV-1 infections in China. Multiple subtypes (A, B, C, E, etc.) were found in Beijing and Shanghai, where HIV infections were still in low level. The sequences of subtype C were less diversive in Xinjiang (p17: 0.0192 +/- 0.0078, C2-V4: 0.0455 +/- 0.0145) than in Yunnan (p17: 0.0279 +/- 0.0102, C2-V4: 0.0482 +/- 0.0171), but all of them clustered in "C" branch in phylogenetic trees. Trafficking of subtype C from Yunnan to Xinjiang was found but had already been reported by others. Compared to subtype C, subtype E was quite divergent (p17: 0.0473 +/- 0.0105, C2-V4: 0.1114 +/- 0.0112) in Yunnan, but no recombination was found in the C2-V4 region of env gene. Highe divergence of subtype B' was found in Henan and the peripheral provinces (p17: 0.0381 +/- 0.0101, C2-V4: 0.0691 +/- 0.0166), which might be attributed to the early epidemics of HIV-1 in these areas (early 1990's). In maternal-child cohort, subtypes B (7/21), C (11/21), E (1/21) and undefined types (2/21) were identified in non-transmitting HIV-1 positive mothers, while only subtype B (7/11) and C (4/11) appeared in transmitting HIV-1 positive mothers. The rate of transmission was 53.8% (7/13) in mothers infected with subtype B and 30.8% (4/13) in those infected with subtype C, but with no significant difference (P = 0.196). The imbalancing distribution of subtypes might be explained by the fact that transfusion or illegal blood would increased mother-to-child transmission on HIV-1 and most of mothers with clade B were infected by illegal blood transfusion in this cohort. In addition, most of the maternal-child pair's sequences clustered in gag or env phylogenetic trees but only a few did disperse among the unrelated patients because children were older (>/= 4 years). CONCLUSION: The characteristics of HIV-1 clade's distribution differed over most parts of China but no difference was demonstrated between subtype B and C in mother-to-child transmission on HIV-1.